Introduction: Several studies have shown a significant amplitude decrement in compound muscle action potentials (CMAPs) on repetitive nerve stimulation (RNS) of muscles involved in amyotrophic lateral sclerosis (ALS).In ALS, muscle wasting preferentially affects the thenar muscles (APB) rather than the hypothenar muscles (ADM). Methods: We performed RNS studies in the APB and ADM muscles of 32 ALS patients to determine whether the effect of RNS differs between the median and ulnar nerves. Results: The decremental responses to RNS were greater in the APB than in the ADM. Reduced CMAP amplitude was negatively correlated with CMAP decrement in median but not in ulnar nerves. Conclusions: The greater CMAP decrement in median nerve is attributable to preferential involvement of the APB in the pathophysiology of ALS or some underlying difference in the biology of the two muscles/nerves. Further investigations will better our understanding of the pathophysiology of ALS. Muscle Nerve, 2012